The IgG Fc receptors on the surface of monocytes, polymorphonuclear leukocytes (PMNs) macrophages, and lymphocytes are essential for IgG antibody-mediated clearance by leukocytes of target cells coated with IgG antibody or of immune complexes containing IgG. Using radiolabeled monomers or oligomers of monoclonal human IgG, we already have evaluated the properties of the Fc receptors on the surface of human monocytes and PMNs, and plan in the future to characterize the Fc receptors on the surface of other leukocyte effectors which may mediate immune clearance of IgG complexed in vivo (especially tissue macrophages and lymphocytes). We have recently demonstrated qualitatively that the Fc receptor function of leukocytes can be depleted as a consequence of interaction with large aggregates of IgG in vitro. In future experiments, using the quantitative binding assays described above, we plan to define the requirements for and mechanism of receptor depletion and to assess the relative capacity of various effectors to recycle or resynthesize receptors to replace those depleted as a consequence of interaction with IgG aggregates. To assess whether a comparable process of receptor depletion can occur during clearance of immune complexes or target cells coated with IgG antibody in vivo, we will compare the number of Fc receptors present on the leukocytes obtained from the peripheral blood or the spleen of patients with diseases characterized by an accelerated rate of IgG-dependent immune clearance (i.e., patients with circulating immune complexes or with immune hemolytic anemia or thrombocytopenia) with the number of Fc receptors present on leukocytes from control donors or patients. In addition, we will evaluate the effect of sera or cells from these patients on the Fc receptors of control leukocytes. Finally using the techniques described, we will assess the effects of corticosteroids and other immunosuppressive agents on the number and affinity of receptors on human leukocytes in vivo and in vitro.